Colorimetric Detection of HER2-Overexpressing-Cancer-Derived Exosomes in Mouse Urine Using Magnetic-Polydiacetylene Nanoparticles.

Abstract

Breast cancer (BC) is a major global health problem, with ≈20-25% of patients overexpressing human epidermal growth factor receptor 2 (HER2), an aggressive marker, yet access to early detection and treatment varies across countries. A low-cost, equipment-free, and easy-to-use polydiacetylene (PDA)-based colorimetric sensor is developed for HER2-overexpressing cancer detection, designed for use in low- and middle-income countries (LMICs). PDA nanoparticles are first prepared through thin-film hydration. Subsequently, hydrophilic magnetic nanoparticles and HER2 antibodies are sequentially conjugated to them. The synthesized HER2-MPDA can be concentrated and separated by a magnetic field while inheriting the optical characteristics of PDA. The specific binding of HER2 antibody in HER2-MPDA to HER2 receptor in HER2-overexpressing exosomes causes a blue-to-red color change by altering the molecular structure of the PDA backbone. This colorimetric sensor can simultaneously separate and detect HER2-overexpressing exosomes. HER2-MPDA can detect HER2-overexpressingexosomes in the culture medium of HER2-overexpressingBCcellsandinmouse urine samples from a HER2-overexpressing BCmousemodel.Itcanselectively isolate and detect only HER2-overexpressingexosomesthroughmagneticseparation, and its detectionlimitisfoundtobe8.5×108particlesmL-1.Thiscolorimetric sensorcanbeusedforpoint-of-carediagnosisofHER2-overexpressing BC in LMICs.